Palmoplantar Pustular Psoriasis Efficacy and Safety With Secukinumab

A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study of Subcutaneous Secukinumab to Demonstrate Efficacy as Assessed by Palmoplantar Pustulosis Psoriasis Area and Severity Index (ppPASI) at 16 Weeks of Treatment, Compared to Placebo, and to Assess Long-term Safety, Tolerability, and Efficacy in Subjects With Moderate to Severe Chronic Palmoplantar Pustular Psoriasis - Amended With an Optional Extension Treatment Period of up to a Total of 148 Weeks

A one year study assessing the efficacy and safety of secukinumab compared with placebo in adult patients with moderate to severe palmoplantar pustular psoriasis - amended with an optional extension treatment period of up to a total of 148 weeks

Study Overview

• Status: Completed
• Conditions: Palmoplantar Pustular Psoriasis
• Intervention / Treatment: Biological: Secukinumab 300mg; Biological: Placebo; Biological: Secukinumab 150mg

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Feldkirch, Austria, A-6807
    • Novartis Investigative Site
  • Graz, Austria, 8036
    • Novartis Investigative Site
  • Linz, Austria, A-4020
    • Novartis Investigative Site
  • Wien, Austria, 1090
    • Novartis Investigative Site
  • Wien, Austria, A-1090
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Liege, Belgium, 4000
    • Novartis Investigative Site
• France
  • Bordeaux Cedex, France, 33075
    • Novartis Investigative Site
  • Clermont Ferrand cedex 1, France, 63003
    • Novartis Investigative Site
  • Martigues, France, 13500
    • Novartis Investigative Site
  • Nice Cedex 3, France, 06202
    • Novartis Investigative Site
  • Paris, France, 75014
    • Novartis Investigative Site
  • Paris, France, 75010
    • Novartis Investigative Site
  • Poitiers, France, 86021
    • Novartis Investigative Site
  • Rouen, France, 76031
    • Novartis Investigative Site
  • Toulouse Cedex, France, 31400
    • Novartis Investigative Site
  • Haute Vienne
    • Limoges cedex, Haute Vienne, France, 87000
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10827
    • Novartis Investigative Site
  • Bochum, Germany, 44803
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Duesseldorf, Germany, D 40225
    • Novartis Investigative Site
  • Freiburg, Germany, 79104
    • Novartis Investigative Site
  • Gera, Germany, 07548
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Greifswald, Germany, 17475
    • Novartis Investigative Site
  • Hamburg, Germany, 20354
    • Novartis Investigative Site
  • Hamburg, Germany, 22391
    • Novartis Investigative Site
  • Hanau, Germany, 63450
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Lubeck, Germany, 23538
    • Novartis Investigative Site
  • Mahlow, Germany, 15831
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • Plauen, Germany, 08529
    • Novartis Investigative Site
  • Recklinghausen, Germany, 45657
    • Novartis Investigative Site
  • Schwerin, Germany, 19055
    • Novartis Investigative Site
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
• Poland
  • Bydgoszcz, Poland, 85-094
    • Novartis Investigative Site
  • Gdansk, Poland, 80-803
    • Novartis Investigative Site
  • Olsztyn, Poland, 10-045
    • Novartis Investigative Site
  • Zabrze, Poland, 41-800
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 107076
    • Novartis Investigative Site
  • Rostov on Don region, Russian Federation, 346880
    • Novartis Investigative Site
  • Ryazan, Russian Federation, 390046
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410012
    • Novartis Investigative Site
• Spain
  • A Coruna, Spain, 15001
    • Novartis Investigative Site
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Madrid, Spain, 28031
    • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Novartis Investigative Site
  • Santa Cruz De Tenerife
    • La Laguna, Santa Cruz De Tenerife, Spain, 38320
      • Novartis Investigative Site
• Sweden
  • Joenkoeping, Sweden, 551 85
    • Novartis Investigative Site
  • Malmo, Sweden, SE-205 02
    • Novartis Investigative Site
  • Stockholm, Sweden, 171 76
    • Novartis Investigative Site
  • Uppsala, Sweden, 751 85
    • Novartis Investigative Site
  • Vastra Gotalands Lan
    • Göteborg, Vastra Gotalands Lan, Sweden, SE-413 45
      • Novartis Investigative Site
• United Kingdom
  • Glasgow, United Kingdom, G11 6NT
    • Novartis Investigative Site
  • Liverpool, United Kingdom, L14 3PE
    • Novartis Investigative Site
  • Newport, United Kingdom, NP20 4SZ
    • Novartis Investigative Site
  • Portsmouth, United Kingdom, PO6 6AD
    • Novartis Investigative Site
  • Wolverhampton, United Kingdom, WV10 0QP
    • Novartis Investigative Site
  • York, United Kingdom, YO31 8HE
    • Novartis Investigative Site
  • London
    • Leytonstone, London, United Kingdom, E11 1NR
      • Novartis Investigative Site
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • Novartis Investigative Site
  • Perthshire
    • Dundee, Perthshire, United Kingdom, DD1 9SY
      • Novartis Investigative Site
  • West Midlands
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Palmoplantar pustular psoriasis for at least 6 months before Randomization

• Moderate to severe palmoplantar pustular psoriasis as defined at Baseline by:

  • ppPASI score of ≥ 12 and
  • DLQI ≥ 10

• Candidate for systemic therapy, defined as having palmoplantar pustular psoriasis inadequately controlled by:

  • Topical treatment, and/or
  • Phototherapy, and/or
  • Previous systemic therapy

Exclusion Criteria:

• Forms of psoriasis other than chronic plaque psoriasis and pustular palmoplantar psoriasis (e.g., erythrodermic, guttate, or generalized pustular psoriasis)
• Drug-induced psoriasis (e.g., new onset or current exacerbation from beta-blockers, calcium channel inhibitors, or lithium) or history of proven contact dermatitis
• Patients not willing to limit UV light exposure (e.g. sunbathing and/or the use of tanning devices) during the course of the study
• Ongoing use of prohibited psoriasis treatments (e.g., topical or systemic corticosteroids, UV therapy). Washout periods detailed in the protocol have to be adhered to
• Previous exposure to any biologic drug directly targeting IL-17 or IL-17 Receptor (e.g., secukinumab, ixekizumab, or brodalumab)
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment and for 16 weeks after stopping treatment
• Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of secukinumab therapy
• Use of any other investigational drugs within 4 weeks of study drug initiation or within a period of 5 half-lives of the investigational treatment, whichever is longer

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secukinumab 300mg; Secukinumab 300mg once weekly at Weeks 1, 2 and 3, thereafter at 4-weekly intervals starting Week 4 until Week 48. In order to maintain the blinding beyond the primary endpoint, placebo was administered at Weeks 17, 18 and 19. For extension period: Secukinumab 300mg at 4-weekly intervals starting Week 52 up to Week 148.	Biological: Secukinumab 300mg; Secukinumab was used as 150 mg pre-filled syringes (PFS) in a double-blinded fashion. Secukinumab 300 mg s.c. (two PFS injections of the 150 mg dose) self-administered; Biological: Placebo; secukinumab placebo s.c. (two PFS injections of placebo) self-administered
Experimental: Secukinumab 150mg; Secukinumab 150mg once weekly at Weeks 1, 2 and 3, thereafter at 4-weekly intervals starting Week 4 until Week 48. In order to maintain the blinding beyond the primary endpoint, placebo was administered at Weeks 17, 18 and 19. For extension period: Secukinumab 150mg at 4-weekly intervals starting Week 52 up to Week 148.	Biological: Placebo; secukinumab placebo s.c. (two PFS injections of placebo) self-administered; Biological: Secukinumab 150mg; secukinumab 150 mg s.c. (one PFS injection of the 150 mg dose + one PFS injection of placebo) self-administered
Placebo Comparator: Placebo; Placebo once weekly at Weeks 1, 2 and 3, thereafter at 4-weekly intervals starting Week 4 until Week 12. Patients who achieved ppPASI 75 at Week 16 remained on placebo treatment Until week 48 and were not eligible to enter the extension. Patients who did not achieve ppPASI 75 at Week 16 were re-randomized to receive Secukinumab 150mg or Secukinumab 300mg from Week 16 onwards up to Week 148.	Biological: Secukinumab 300mg; Secukinumab was used as 150 mg pre-filled syringes (PFS) in a double-blinded fashion. Secukinumab 300 mg s.c. (two PFS injections of the 150 mg dose) self-administered; Biological: Placebo; secukinumab placebo s.c. (two PFS injections of placebo) self-administered; Biological: Secukinumab 150mg; secukinumab 150 mg s.c. (one PFS injection of the 150 mg dose + one PFS injection of placebo) self-administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With ppPASI 75 Response at Week 16 (Period 1)	The primary endpoint was assessed by the palmoplantar pustulosis Psoriasis Area and Severity Index 75 (ppPASI 75). The percentage of subjects who achieved a 75% reduction in ppPASI score from Baseline to Week 16 was measured. The ppPASI is a modification of the PASI score and adjusted for palmoplantar pustular psoriasis by classifying and scoring erythema, scaling (desquamation) and pustules/vesicles. Both palms and both plants are scored from 0 to 4. The extent of involvement of each region of the body is scored from 0 to 6. The total ppPASI score can range from a lower level of 0, corresponding to no signs of psoriasis, up to a maximum of 72.	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ppPASI: Absolute Change From Baseline to Week 16	A secondary endpoint was assessed by the palmoplantar pustulosis Psoriasis Area and Severity Index (ppPASI). The mean change of ppPASI score from Baseline to Week 16 was measured. The ppPASI is a modification of the PASI score and adjusted for palmoplantar pustular psoriasis by classifying and scoring erythema, scaling (desquamation) and pustules/vesicles. Both palms and both plants are scored from 0 to 4. The extent of involvement of each region is scored from 0 to 6. The total ppPASI score can range from a lower level of 0, corresponding to no signs of psoriasis, up to a maximum of 72.	Baseline to Week 16
Percentage of Participants With ppPASI 75 Response Over Time (Period 1)	A secondary endpoint was assessed as response rate of patients to treatment measured by the palmoplantar pustulosis Psoriasis Area and Severity Index 75 (ppPASI 75). The percentage of subjects who achieve a 75% reduction in ppPASI score from Baseline to each post-baseline visit is measured. The ppPASI is a modification of the PASI score and adjusted for palmoplantar pustular psoriasis by classifying and scoring erythema, scaling (desquamation) and pustules/vesicles. Both palms and both plants are scored from 0 to 4. The extent of involvement of each region of the body is scored from 0 to 6. The total ppPASI score can range from a lower level of 0, corresponding to no signs of psoriasis, up to a maximum of 72.	Baseline to Week 16
Percentage of Participants With ppPASI 75 Response Over Time (Period 2)	A secondary endpoint was assessed as response rate of patients to treatment measured by the palmoplantar pustulosis Psoriasis Area and Severity Index 75 (ppPASI 75). The percentage of subjects who achieve a 75% reduction in ppPASI score from Baseline to each post-baseline visit is measured. The ppPASI is a modification of the PASI score and adjusted for palmoplantar pustular psoriasis by classifying and scoring erythema, scaling (desquamation) and pustules/vesicles. Both palms and both plants are scored from 0 to 4. The extent of involvement of each region of the body is scored from 0 to 6. The total ppPASI score can range from a lower level of 0, corresponding to no signs of psoriasis, up to a maximum of 72.	Week 16 to Week 52
Percentage of Participants With ppPASI 75 Response Over Time (Extension Period)	A secondary endpoint was assessed as response rate of patients to treatment measured by the palmoplantar pustulosis Psoriasis Area and Severity Index 75 (ppPASI 75). The percentage of subjects who achieved a 75% reduction in ppPASI score from Baseline to each post-baseline visit was measured. The ppPASI is a modification of the PASI score and adjusted for palmoplantar pustular psoriasis by classifying and scoring erythema, scaling (desquamation) and pustules/vesicles. Both palms and both plants are scored from 0 to 4. The extent of involvement of each region of the body is scored from 0 to 6. The total ppPASI score can range from a lower level of 0, corresponding to no signs of psoriasis, up to a maximum of 72.	Week 52 to Week 148
Percentage of Participants With Most Frequent Adverse Events - Period 1 (Patient's Safety)	Most frequent (at least 5% in any of the AIN457 groups) Adverse Events	Baseline to Week 16 (Period 1)
Percentage of Participants With Most Frequent Adverse Events - Period 2 (Patient's Safety)	Most frequent (at least 5% in any of the AIN457 groups) Adverse Events	Week 16 to Week 52 (Period 2)
Percentage of Participants With Most Frequent Adverse Events - Extension Period (Patient's Safety)	Most frequent (at least 5% in any of the AIN457 groups) Adverse Events	Week 52 to Week 148 (extension period)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2013
• Primary Completion (Actual): November 24, 2014
• Study Completion (Actual): May 31, 2017

Study Registration Dates

• First Submitted: December 8, 2013
• First Submitted That Met QC Criteria: December 8, 2013
• First Posted (Estimate): December 11, 2013

Study Record Updates

• Last Update Posted (Actual): January 4, 2019
• Last Update Submitted That Met QC Criteria: January 1, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: palmoplantar, pustular, psoriasis
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457A3301; 2013-003086-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com